TITLE

Bile-acid-induced cell injury and protection

AUTHOR(S)
Perez, Maria J.; Briz, Oscar; Matsuzaki, Yasushi
PUB. DATE
April 2009
SOURCE
World Journal of Gastroenterology;4/14/2009, Vol. 15 Issue 14, p1677
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids (BAs) in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyl-N-methylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties.
ACCESSION #
42838499

 

Related Articles

  • Eupatilin attenuates bile acid-induced hepatocyte apoptosis. Park, Su Cheol; Yoon, Jung-Hwan; Kim, Won; Gwak, Geum-Youn; Kim, Kang Mo; Lee, Sung-Hee; Lee, Soo-Mi; Lee, Hyo-Suk // Journal of Gastroenterology;Aug2006, Vol. 41 Issue 8, p772 

    In cases of cholestasis, bile acids induce hepatocyte apoptosis by activating death receptor-mediated apoptotic signaling cascades. Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredient found in Artemisia asiatica and exhibits cytoprotective effects against...

  • Bile Acids Affect Liver Mitochondrial Bioenergetics: Possible Relevance for Cholestasis Therapy. Rolo, Anabela P.; Oliveira, Paulo J.; Moreno, António J. M.; Palmeira, Carlos M. // Toxicological Sciences;Sep2000, Vol. 57 Issue 1, p177 

    It has been pointed out that intracellular accumulation of bile acids cause hepatocyte injury in cholestatic disease process. This study was aimed to test if cytotoxicity of these compounds is mediated through mitochondria dysfunction. Bile acids effects on isolated rat liver mitochondrial were...

  • Modulation of Hepatocyte Apoptosis: Cross-talk Between Bile Acids and Nuclear Steroid Receptors. Solá, S.; Amaral, J. D.; Aranha, M. M.; Steer, C. J.; Rodrigues, C. M. P. // Current Medicinal Chemistry;2006, Vol. 13 Issue 25, p3039 

    The efficient removal of unwanted cells, such as senescent, damaged, mutated or infected cells is crucial for the maintenance of normal liver function. In fact, apoptosis has emerged as a potential contributor to the pathogenesis of a number of hepatic disorders, such as viral hepatitis,...

  • Interlobular Bile Duct Cholestatic Disease is Aberrant Cytokeratin by Hepatocytes Loss in Pediatric Associated with 7 Expression. Ernst, Linda M.; Spinner, Nancy B.; Piccoli, David A.; Mauger, Joanne; Russo, Pierre // Pediatric & Developmental Pathology;Sep/Oct2007, Vol. 10 Issue 5, p383 

    The objective of this study was to determine whether aberrant hepatic expression of cytokeratin 7 (CK7) and/or other putative stem cell markers is seen in pediatric cholestatic diseases. Eighteen liver biopsies and 14 liver explants from pediatric patients with extrahepatic biliary atresia...

  • Reactive oxygen species production in association with suberization: evidence for an NADPH‐dependent oxidase. Razem, Fawzi A.; Bernards, Mark A. // Journal of Experimental Botany;Mar2003, Vol. 54 Issue 384, p935 

    In response to wounding, potato tubers generate reactive oxygen species (ROS) in association with suberization. Immediately following wounding, an initial burst of ROS occurs, reaching a maximum within 30 to 60 min. In addition to this initial oxidative burst, at least three other massive bursts...

  • Oxidative stress profile in the post-operative patients with biliary atresia. Asakawa, Takahiro; Tanaka, Yoshiaki; Asagiri, Kimio; Kobayashi, Hidefumi; Tanikawa, Ken; Yagi, Minoru // Pediatric Surgery International;Jan2009, Vol. 25 Issue 1, p93 

    Background and Purpose: Many post-operative patients with biliary atresia (BA) suffer from liver dysfunction, such as chronic inflammation even without jaundice after a Kasai's hepatic portoenterostomy.Methods: The presence and degree of oxidative stress were evaluated...

  • FXR as a Drug Target to Treat Progressive Familial Intrahepatic Cholestasis. Ivy, Kathryn Stevens // Vanderbilt Undergraduate Research Journal;Spring2015, Vol. 10, p1 

    Progressive Familial Intrahepatic Cholestasis (PFIC) is a condition that results in the cirrhosis of the liver and eventually liver failure due to impaired bile flow. If left untreated and even if treated, PFIC will result usually in an early death. While the causes of this disease vary, all...

  • Physiology of bile secretion. Esteller, Alejandro; Jirsa, Milan; Liqing Yu // World Journal of Gastroenterology;10/7/2008, Vol. 14 Issue 37, p5641 

    The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition...

  • The Expression Levels of Plasma Membrane Transporters in the Cholestatic Liver of Patients Undergoing Biliary Drainage and Their Association With the Impairment of Biliary Secretory Function. Shoda, Junichi; Kano, Masahito; Oda, Koji; Kamiya, Junichi; Nimura, Yuji; Suzuki, Hiroshi; Sugiyama, Yuichi; Miyazaki, Hiroshi; Todoroki, Takeski; Stengelin, Siegfried; Kramer, Werner; Matsuzaki, Yasushi; Tanaka, Naomi // American Journal of Gastroenterology;Dec2001, Vol. 96 Issue 12, p3368 

    OBJECTIVES: Percutaneous transhepatic biliary drainage (PTBD) has been believed to reduce hyperbilirubinemia in patients with obstructive cholestasis and to lessen liver injury through bile acid retention. The efficacy may be closely related to the capability of cholestatic liver to produce and...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics